tyrosine kinase, and activation of the kinase is re- 
quired for all subsequent events associated with 
CD28 activation. However, immunoprecipitation of 
CD28 from activated T cells has failed to coprecipi- 
tate a tyrosine kinase but has allowed the identifica- 
tion of a novel low-molecular-weight protein that 
specifically associates with CD28. Work to identify 
the mechanism of tyrosine kinase activation by 
CD28 is under way. 
The natural ligand for CD28, B7, is expressed on 
activated antigen-presenting cells. In collaboration 
with Dr. Peter Linsley, Dr. Thompson's group has 
succeeded in demonstrating that B7-dependent T 
cell activation is required for the initiation of allo- 
graft rejection in vivo. These studies, and those of 
several other groups, demonstrate the importance of 
CD28 activation in the initiation of some forms of 
immune response. Studies are under way to deter- 
mine whether additional co-stimulatory pathways 
exist and, if so, what role they play in regulating the 
subsequent immune response. 
The Bursa of Fabricius as a Model System 
for Study of Lymphoid Development 
The avian bursa of Fabricius provides a unique 
organ for the study of lineage-specific development 
in a multicellular organism. In the chicken, B cells 
develop in a single wave, beginning with commit- 
ment of progenitor cells to B cell differentiation be- 
tween days 10-15 of embryogenesis. By day 18 all 
lymphoid progenitor cells capable of B cell differ- 
entiation have migrated to the bursa of Fabricius. 
Once these cells enter the bursa, they begin to grow 
exponentially and to populate the bursal follicles. 
Between day 18 of embryogenesis and 4 weeks of 
age, B cells undergo a stage of bursal-dependent dif- 
ferentiation, and by the end of this period, chickens 
are able to mount primary immune responses 
against virtually all antigens. At 4 weeks of age, suf- 
ficient numbers of B cells have migrated from the 
bursa to peripheral lymphoid organs so that even if 
the bird is bursectomized, the B cell immune system 
is maintained. 
Over the past several years. Dr. Thompson and his 
colleagues have attempted to identify molecules 
that allow B cells to home to the bursa of Fabricius 
and be retained there. In collaboration with Dr. John 
Lowe (HHMI, University of Michigan), they have 
found that each of the stages of avian B cell develop- 
ment defined above is associated with a profound 
alteration in the glycosylation of the proteins and 
lipids on the surface of the cell. These changes in 
glycosylation are required for cells to 1) migrate to 
the bursa, 2) be retained within the bursal follicle, 
and 3) migrate to the peripheral lymphoid organs 
following completion of the bursal-dependent 
phase of differentiation. How this differential 
glycosylation is regulated is now under active 
investigation. 
Unlike mammals, the chicken immunoglobulin 
(Ig) loci contain only single variable and joining 
segments capable of undergoing rearrangement. To 
create an immunological repertoire, chickens must 
diversify the coding sequence of the Ig light-chain 
(IgL) and heavy-chain (Ign) V gene segments during 
development. This diversification occurs during the 
bursal-dependent phase of B cell development. Ig 
gene diversification is limited to the rearranged V 
gene segment and occurs by intrachromosomal gene 
conversion using V-region pseudogenes as sequence 
donors. 
The laboratory has been able to demonstrate some 
novel features of this somatic gene conversion pro- 
cess. First, gene conversion appears to be dependent 
upon transcription of recipient sequences; second, 
cells that undergo gene conversion are proficient in 
homologous recombination; and third, gene con- 
version is restricted to the Ig loci. 
To test whether Ig gene conversion is related to Ig 
rearrangement, the laboratory examined cells un- 
dergoing IgL gene conversion for the expression of 
genes required for Ig recombination and found that 
one gene, recombination-activating gene 2 {RAG- 
2) , is selectively expressed during the bursal stage 
of B cell development. However, when the RAG-2 
gene was eliminated from a bursal cell line that con- 
stitutively undergoes Ig gene conversion in culture, 
the cell line retained the ability to undergo Ig gene 
conversion. Currently the laboratory is raising anti- 
sera to the RAG-2 protein in order to examine its 
role in the bursal-dependent phase of B cell develop- 
ment. (Studies of the regulation of Ig gene conver- 
sion are funded in part by a grant from the National 
Institutes of Health.) 
Dr. Thompson is also Associate Professor of 
Medicine and of Microbiology and Immunology 
at the University of Michigan Medical School and 
a member of the Cell and Molecular Biology grad- 
uate program at the University of Michigan. 
Books and Chapters of Books 
Thompson, C.B., Jackson, K.M., Turka, L.A., Mit- 
chell, B.S., and June, C.H. 1991. Development of 
an in vitro model system to study the physiologic 
effects and toxicities of immunosuppressants. In 
In Vitro Toxicology: Mechanisms and New Tech- 
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